The need to consume adequate dietary protein to preserve physical function during ageing is well recognized. However, the effect of protein intakes on glucose metabolism is still intensively debated. During age-related oestrogen withdrawal at the time of the menopause, it is known that glucose homeostasis may be impaired but the influence of dietary protein levels in this context is unknown. The aim of the present study is to elucidate the individual and interactive effects of oestrogen deficiency and suboptimal protein intake on glucose homeostasis in a preclinical model involving ovariectomy (OVX) and a 13-week period of a moderately reduced protein intake in 7-month-old ageing rats. To investigate mechanisms of action acting via the pancreas-liver-muscle axis, fasting circulating levels of insulin, glucagon, IGF-1, FGF21 and glycemia were measured. The hepatic lipid infiltration and the protein expression of GLUT4 in the gastrocnemius were analyzed. The gene expression of some hepatokines, myokines and lipid storage/oxidation related transcription factors were quantified in the liver and the gastrocnemius. We show that, regardless of the oestrogen status, moderate dietary protein restriction increases fasting glycaemia without modifying insulinemia, body weight gain and composition. This fasting hyperglycaemia is associated with oestrogen status-specific metabolic alterations in the muscle and liver. In oestrogen-replete (SHAM) rats, GLUT4 was down-regulated in skeletal muscle while in oestrogen-deficient (OVX) rats, hepatic stress-associated hyperglucagonaemia and high serum FGF21 were observed. These findings highlight the importance of meeting dietary protein needs to avoid disturbances in glucose homeostasis in ageing female rats with or without oestrogen withdrawal.
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